Changes in neuronal excitability serve as a mechanism of long-term memory for operant conditioning

Abstract

Learning can lead to changes in the intrinsic excitability of neurons. However, it is unclear to what extent these changes persist and what role they play in the expression of memory. Here, we report that in vitro analogues of operant conditioning produce a long-term (24 h) increase in the excitability of an identified neuron (B51) critical for the expression of feeding in Aplysia. This increase in excitability, which is cAMP dependent, contributes to the associative modification of the feeding circuitry, providing a mechanism for long-term memory storage.

Effects of aversive stimuli beyond defensive neural circuits: Reduced excitability in an identified neuron critical for feeding in Aplysia

“…B51 appears to influence the nature of the motor output: suprathreshold activation of B51 promotes the expression of ingestive BMPs, whereas hyperpolarization of B51 prevents their occurrence (Nargeot et al 1999a,b). Notably, an increase in B51 excitability has been associated with the increased number of ingestive BMPs in vitro and bites in vivo produced by operant reward learning (Nargeot et al 1999a,b;Brembs et al 2002;Mozzachiodi et al 2008). Therefore, B51 represents a putative site of plasticity underlying the suppression of feeding induced by LTS training.…”

“…This variability prevents comparison of data across experiments (e.g., controls in Figs. 1B2 and 3B2) and requires treatment vs. control comparisons to isolate/exclude treatment-dependent effects (Brembs et al 2002;Lorenzetti et al 2006;Mozzachiodi et al 2008).…”

Implication of dopaminergic modulation in operant reward learning and the induction of compulsive-like feeding behavior inAplysia

“…Cold Spring Harbor Laboratory Press on May 11, 2018 -Published by learnmem.cshlp.org Downloaded from Operant conditioning of Aplysia feeding was previously found to modify the animal's decision-making capability for the autonomous selection and initiation of radula feeding-related actions, leading to a long-lasting increase in the frequency and regularity of ingestive (biting) movement occurrences (Nargeot and Simmers 2012). In the present study, the in vitro analog of this operant conditioning used to explore the role of contingentdependent DA release in the reinforcement pathway was similar to that initially developed to analyze the contribution of rewarding esophageal nerve input to selecting the type of radula motor pattern produced (Nargeot et al 1997;Mozzachiodi et al 2008). In this analog of learning the contingent stimulation of En.2 (10 Hz, 6 sec, 8 -9 V), which was delivered at the end of the retraction phase of each spontaneous ingestive pattern, was found to selectively favor the continued expression of the rewarded pattern.…”

“…Importantly, moreover, the induction of these network and cellular changes was blocked by an Aplysia D1-like receptor antagonist, flupenthixol, thereby indicating a fundamental role for dopamine in mediating the operant plasticity (Barbas et al 2006). Several earlier studies have provided substantial evidence that esophageal input nerve fibers mediate food-reward processes in Aplysia: (1) food stimuli that contributed to the reinforcing process in different forms of both operant and classical conditioning were found to elicit transient esophageal nerve activity Lechner et al 2000;Brembs et al 2002); (2) such appetitive associative learning was impaired by lesions to these afferent pathways; (3) in in vitro analogs of this associative-learning phasic En.2 electrical stimulation to mimic food signals conveyed in vivo was found to reproduce various facets of the motor circuit-and/or cell-wide plasticity resulting from learning (Nargeot et al 1999a,b;Brembs et al 2002Brembs et al , 2004Reyes et al 2005;Mozzachiodi et al 2008). In addition, there is considerable data indicating that the esophageal nerve terminals release DA: (1) histofluorescence analyses showed these bilateral nerves to be rich in DA-containing fibers and En.2 was also found to be immunoreactive to tyrosine hydroxylase (Kabotyanski et al 1998;Martí-nez-Rubio et al 2009); (2) in vitro exposure to a DA antagonist, methylergonovine, blocked the monosynaptic actions of esophageal inputs on identified neurons (e.g., B51; see below) of the buccal CPG circuit (Nargeot et al 1999c) and transient iontophoretic application of DA to such neurons in culture reproduced their membrane responses to esophageal nerve stimulation in situ (Brembs et al 2002;Lorenzetti et al 2008).…”

“…In this analog of learning the contingent stimulation of En.2 (10 Hz, 6 sec, 8 -9 V), which was delivered at the end of the retraction phase of each spontaneous ingestive pattern, was found to selectively favor the continued expression of the rewarded pattern. Moreover, this plasticity was associated with a DA-dependent enhancement of plateauing properties in buccal network neuron B51, which, in turn, during the retraction phase of pattern genesis modifies the decision process for the type of radula output expressed, biasing motor pattern selection toward ingestive (i.e., biting) rather than egestive pattern genesis (Nargeot et al 1999a,b,c;Brembs et al 2002;Mozzachiodi et al 2008). Although an increased rate of radula pattern genesis was also observed in this analog of operant conditioning, the underlying cellular mechanisms and the ability of contingent En.2 stimulation and DA release to transform motor pattern production from sporadic to stereotyped rhythmogenesis, as addressed in the present study, had not been previously investigated.…”